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KMID : 0828520110150030144
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Journal of the Korean Geriatrics Society
2011 Volume.15 No. 3 p.144 ~ p.161
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Gene Expression Analysis of The Human Astrocytoma Cell After Aβ25-35 Stimulation Followed by Ibuprofen Administration
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Choi Young-Sook
Eun Jung-Woo
Nam Suk-Woo
Kim Sang-Ho
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Abstract
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Background: The molecular events leading to the development of sporadic late-onset Alzheimer`s disease have not been defined. We investigated global gene expression analysis of ibuprofen on the amyloid-β25-35(Aβ25-35)-stimulated human astrocytoma cell.
Methods: U373MG, a human astrocytoma cell line, was incubated with 25 μM of aggregated Aβ25-35 or aggregated Aβ25-35 plus 100 μM ibuprofen at 37℃ for 24 hours. Cells treated with ibuprofen alone were used as negative control. Differential gene expression analysis was carried out with Illumina human whole genome microarray. Real-time reverse transcriptase(RT)-PCR was also done for the validation of gene expression changes. After Welch`s T-test, significant subset of outlier genes were identified by an expression change cut-off 1.5 fold, p<0.05. Kyoto Encyclopedia of Genes and Genomes database was employed for cellular signaling pathway analysis.
Results: A total of 371 differentially expressed genes were identified from 16,692 detectable signals in Aβ25-35 peptide stimulated U373MG cells; 182 up-regulated genes with 21 biological pathways including biosynthesis of steroid, PPAR signaling pathway and focal adhesion, 189 down-regulated genes with 14 biological pathways including TGF-beta signaling pathway, axon guidance and MAPK signaling pathway. Ibuprofen suppressed the up-regulated expression of immunity/inflammation(especially, SERPINE1), signal pathway, metabolism, cancer-related genes. Expression of microarray data was confirmed by real-time RT-PCR.
Conclusion: Aggregated Aβ25-35 induces expression of widespread transcriptional alterations, namely 21 functional groups 182 up-regulated genes and 14 functional groups 189 down-regulated genes in U373MG cells. Ibuprofen suppressed Aβ25-35-induced increase of global changes in transcription of sets of genes especially immunity/inflammation, signal pathway, metabolism and cancer-related genes."
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KEYWORD
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Alzheimer, Amyloid beta-Protein, cDNA Microarrays, Ibuprofen, NSAIDs
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